Project Summary/Abstract Improvements in the scalability and timeliness of traditional clinical research trial models increasingly rely upon incorporation of added sources of `Real World Data' (RWD) ? data from electronic health record systems (EHRs), observational studies and disease registries, and patient and/or caregiver report. Similarly, observational, post-marketing drug safety surveillance efforts also remain limited in capability and cost- effectiveness until these other important, added sources of RWD are able to be incorporated in a facile, efficient, and timely fashion. Conventional data interchange standards such as HL7 v3 and Clinical Data Interchange Standards Consortium (CDISC) standards, e.g. Operational Data Model (ODM-XML), Define-XML, Data-XML, are not well-adopted, often limited in suitability, and not focused on modern API-based interchange of RWD. The overall goal of this proposed project is the development and demonstration of new FHIR extensions, profiles, resources, and implementations that support FDA 21 CFR 11-compliant workflows for disease registry-based information exchange, thereby providing important advantages over current, non-FHIR- based approaches for conducting such studies. We leverage the expertise and extensive experience of the participating investigators and institutions, who are collecting and using RWD for Phase IV safety surveillance activities, and who are already utilizing FHIR for warehousing of this data. Specifically, we target two high- value, readily achievable, and broadly relevant areas for application of FHIR data interchange standards to this domain: (1) Incorporation of patient-reported outcomes (PRO) data into 21 CFR 11-compliant workflows using FHIR, and (2) Enablement of a standardized approach within FHIR to query and deliver reproducible data sets supporting 21 CFR11-compliant analyses suitable for post-marketing safety surveillance. As part of this project, we will submit these improvements to HL7 for incorporation into FHIR, make our implementations publicly available, and also produce a white paper summarizing the work accomplished, potential paths forward for using the products, and best practices or concerns that should be addressed in subsequent work.